1. Field of Invention
The present invention relates to formulations for inhibiting Cathepsin G, Cathepsin S, Cathepsin B, Cathepsin L, Butyryl Cholinesterase, Peptidase HIV-1, and NF-kB comprising processed Morinda citrifolia products and methods for administering such.
2. Background
Aspartic peptidases have received enormous interest because of their significant roles in human diseases like involvement of renin in hypertension, cathepsin D in metastasis of breast cancer, β-Secretase in Alzheimer's Disease, plasmepsins in malaria, HIV-1 peptidase in acquired immune deficiency syndrome, and secreted aspartic peptidases in candidal infections. The HIV-1 peptidase is required for the replication and further infection by the virus. Effort has taken place for several years to understand the properties of this enzyme, because it has potential as a drug target to control HIV-1.
Elevated cathepsin enzyme activity in serum or the extracellular matrix is often related to a number of pathological conditions. Cathepsin-mediated diseases include: Alzheimer's, numerous types of cancer, autoimmune related diseases like arthritis and the accelerated breakdown of bone structure seen with osteoporosis. Up-regulated cathepsin B and L activity has been linked to several types of cancer. These include cancer of the colon, pancreas, ovaries, breast, lung and skin (melanoma). Up-regulation of cathepsin K has been shown un lung tumors. Increased cathepsin K activity has also been linked to degenerative bone diseases including osteoporosis and post-menopausal osteoporosis.
The cathepsins family contains members of the lysosomal cysteine protease, members of the serine protease (cathepsin A, G) and aspartic protease (cathepsin D, E). These enzymes exist in their processed form as disulfide-linked heavy and light chain subunits with molecular weights ranging from 20-35 kDa. Cathepsin C is the noted exception, existing as an oligomeric enzyme with a MW -200 kDa. Initially synthesized as inactive zymogens, they are post-transitionally processed into their active configurations after passing through the endoplasmic reticulum and subsequent incorporation into the acidic environment of the lysosomes.
In resting cells, cytoplasmic location of the nuclear transcription factor NF-kB is bound by an inhibitory subunits IkB; binding of IkB effectively masks the nuclear localization sequences present on the P50 and P65 subunits of NF-kB, preventing nuclear translocation. It appears that upon cellular stimulation, a signal transduction pathway is activated leading to phosphorylation of key serine residues in the IkB polypeptide whereupon the NF-kB-IkB complex dissociates, IkB is rapidly degraded, and the unmasked nuclear localization signal allows NF-kB to translocate into nucleus and activate the transcription of specific genes. It is known that NF-kB regulates many proinflammatory and prothrombic factors produced by activated leukocytes. NF-kB represents a master regulator of inflammation and is, therefore, an attractive target for drug development.